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| Status |
Public on Sep 04, 2024 |
| Title |
dact1/2 modifies noncanonical Wnt signaling and calpain 8 expression to regulate convergent extension and craniofacial development |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Wnt signaling plays a fundamental role in the initial patterning and development of the embryo, including in the regulation of convergent extension during gastrulation and the establishment of the dorsal axis. Further, Wnt signaling is a crucial regulator of craniofacial morphogenesis. The relationship between early embryo patterning and craniofacial outcomes warrants further study. The adapter proteins Dact1 and Dact2 modulate the Wnt signaling pathway through binding to Disheveled, however, the distinct roles of Dact1 and Dact2 during embryogenesis remain to be fully elucidated. In this study, we investigated the spatiotemporal gene expression patterns of dact1 and dact2 during zebrafish embryogenesis, revealing both shared and unique domains of expression. We found that both dact1 and dact2 contribute to axis extension, with compound mutants exhibiting a similar convergent extension defect and craniofacial phenotype to the wnt11f2/slb mutant. Utilizing single-cell RNAseq and gpc4-/- zebrafish, a convergent extension mutant with an opposite craniofacial phenotype, we identified dact1/2 specific roles during early development. Using this subtractive approach, we discovered a novel role for dact1/2 in regulating the mRNA expression of the classical calpain, capn8, suggesting a previously unappreciated role of calcium-dependent proteolysis during embryogenesis. Taken together, our findings highlight the distinct and overlapping roles of dact1 and dact2 in embryonic craniofacial development, providing new insights into the multifaceted regulation of Wnt signaling.
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| Overall design |
Single-cell RNA sequencing (scRNA-seq) analyses were performed on 10 zebrafish embryos (4 WT, 3 dact1-/-;dact2-/- compound mutant, and 3 gpc4-/- mutant embryos) harvested at the 3 somite stage, to assess transcriptomic perturbations during development induced by deletion of dact1/2.
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| Web link |
https://elifesciences.org/reviewed-preprints/91648
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| Contributor(s) |
Carroll SH, Schafer S, Kawasaki K, Tsimbal C, Julé AM, Hallett S, Li E, Liao EC |
| Citation(s) |
37986847 |
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| Submission date |
Aug 07, 2023 |
| Last update date |
Sep 05, 2024 |
| Contact name |
Amélie M Julé |
| Organization name |
Kennedy Institute of Rheumatology (KIR)
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| Lab |
Computational and Single Cell Genomics Group
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| Street address |
Roosevelt Drive, Headington
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| City |
Oxford |
| ZIP/Postal code |
OX3 7FY |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
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| Samples (10)
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| GSM7689206 |
Zebrafish, 3 somite stage embryo, WT, replicate 1 |
| GSM7689207 |
Zebrafish, 3 somite stage embryo, WT, replicate 2 |
| GSM7689208 |
Zebrafish, 3 somite stage embryo, dact1-/-;dact2-/- compound mutant, replicate 1 |
| GSM7689209 |
Zebrafish, 3 somite stage embryo, gpc4 mutant, replicate 1 |
| GSM7689210 |
Zebrafish, 3 somite stage embryo, WT, replicate 3 |
| GSM7689211 |
Zebrafish, 3 somite stage embryo, dact1-/-;dact2-/- compound mutant, replicate 2 |
| GSM7689212 |
Zebrafish, 3 somite stage embryo, gpc4 mutant, replicate 2 |
| GSM7689213 |
Zebrafish, 3 somite stage embryo, WT, replicate 4 |
| GSM7689214 |
Zebrafish, 3 somite stage embryo, dact1-/-;dact2-/- compound mutant, replicate 3 |
| GSM7689215 |
Zebrafish, 3 somite stage embryo, gpc4 mutant, replicate 3 |
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| Relations |
| BioProject |
PRJNA1003061 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240264_RAW.tar |
150.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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